Modeling dioxygen binding to the non-heme iron-containing enzymes

The structures and properties of the complexes formed upon binding the oxygen molecule to the iron sites in non‐heme 2‐oxoglutarate‐dependent enzymes are characterized by QM(CASSCF)/MM and density functional theory (DFT) calculations. Molecular models for the calculations are constructed following the crystal structure of hypoxia‐inducible factor asparaginyl hydroxylase (FIH‐1). DFT calculations for the 37‐atomic cluster have been carried out at the B3LYP(LANL2DZdp) level. The flexible effective fragment potential method is used as a combined quantum mechanical–molecular mechanical (QM/MM) technique to characterize the fragment of the enzymatic system, including 1,758 atoms in the MM part and 27 atoms in the QM part. In these calculations, the CASSCF(LANL2DZdp) approach is applied in the QM subsystem, and AMBER force field parameters are used in the MM subsystem. With both approaches, equilibrium geometry configurations have been located for different spin states of the system. In DFT calculations, the order of the states is as follows: septet, triplet (+7.7 kcal/mol), quintet (+10.7 kcal/mol). Geometry configurations correspond to the end‐on structures with no evidences of electron transfer from Fe(II) to molecular oxygen. In contrast, QM(CASSCF)/MM calculations predict the quintet state as the lowest one, while the septet structure has slightly (<2 kcal/mol) higher energy, and the triplet state is considerably more energetic. In QM/MM calculations, in both quintet and septet states, the electronic configurations show considerable electron charge transfer from iron to oxygen, and the oxidation state of iron in the metal binding site can be characterized as Fe(III). © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006